Hematopoietic tissue is constantly renewed through the proliferation and differentiation of stem cells residing in the bone marrow in close contact with multiple adherent (stromal) cells that comprise the hematopoietic microenvironment (HM). In vitro stromal cells form fibroblast colonies (CFU-F) which, under defined conditions support long-term bone marrow growth of primitive hematopoietic stem cells (LTBMC-long term bone marrow cultures, or Dexter-type cultures). The interactions between the hematopoietic cells and the microenvironment are not well understood, due to the cellular heterogeneity of this microenvironment and to the difficulties in isolating homogeneous populations of its components for genetic and functional studies. The development of the PCR technology has enabled detection of growth factor transcripts in stromal marrow fibroblasts, suggesting that, via these cytokines, these cells play an important role in hematopoiesis in mammals in vivo.
Different experimental approaches have revealed that the protooncogene c-myb plays an important role in regulating not only hematopoietic cell growth, but also proliferation of non-hematopoietic cells. Treatment with synthetic c-myb antisense oligodeoxynucleotides inhibits formation of colonies derived from normal hematopoietic progenitors. Inactivation of the endogenous c-myb gene by homologous recombination in mouse embryonic stem cells drastically impairs liver hematopoiesis. There remains a need to determine the role and effect of c-myb regulation on other cell functions.